Ovarian cancer is second only to breast cancer as the most common cause of death from gynecological malignancy in women in this country. The principal objective of this project is to identify antigens or markers of ovarian tumors, which can be used in an immunodiagnostic assay for the detection of early ovarian cancer. Xenogeneic antisera have been used to identify two antigens (OvC-1 and OvC-2) present in the extracts of ovarian tumors, and these antigens have been partially purified. In addition, a panel of mouse monoclonal antibodies has been produced by immunization of mice with ovarian and endometrial cancer cell lines. Most of the antigens detected had rather wide-spread distribution; however, a few antibodies detected antigens with more restricted distributions, and these antibodies were selected for further analysis. MD 144 antigen was detected on a single ovarian cancer cell line and has the biochemical properties of a lipid. MF 61 antigen was detected on one of eight ovarian cancer and six of 16 renal cancer cell lines but not on other cell lines tested. It was also detected in the follicles of the thyroid and in uterine glandular epithelial cells. MH 99 was detected on three of eight ovarian cancer, three of seven colon cancer and a number of other epithelial cancer cell lines. It is also present in normal pancreas and uterine epithelia but not in other normal tissues. MF 116 was detected on two of eight ovarian cancer, six of 16 renal cancer, and a few other epithelial cancer cell lines. It was not detected in any normal tissue tested. This antigen is readily shed into the culture supernatant, and this form has a 105,000 Mr. This antigen may be useful in the immunodiagnosis and monitoring of ovarian cancer.